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Many studies highlight the remarkable plasticity demonstrated by spinal circuits following an incomplete spinal cord injury (SCI). Such plasticity can contribute to improvements in volitional motor recovery, such as walking function, although similar mechanisms underlying this recovery may also contribute to the manifestation of exaggerated responses to afferent input, or spastic behaviors. Rehabilitation interventions directed toward augmenting spinal excitability have shown some initial success in improving locomotor function. However, the potential effects of these strategies on involuntary motor behaviors may be of concern. In this article, we provide a brief review of the mechanisms underlying recovery of volitional function and exaggerated reflexes, and the potential overlap between these changes. We then highlight findings from studies that explore changes in spinal excitability during volitional movement in controlled conditions, as well as altered kinematic and behavioral performance during functional tasks. The initial focus will be directed toward recovery of reflex and volitional behaviors following incomplete SCI, followed by recent work elucidating neurophysiological mechanisms underlying patterns of static and dynamic muscle activation following chronic incomplete SCI during primarily single-joint movements. We will then transition to studies of locomotor function and the role of altered spinal integration following incomplete SCI, including enhanced excitability of specific spinal circuits with physical and pharmacological interventions that can modulate locomotor output. The effects of previous and newly developed strategies will need to focus on changes in both volitional function and involuntary spastic reflexes for the successful translation of effective therapies to the clinical setting.

This study tested the hypothesis that high cardiorespiratory fitness (peak oxygen uptake) preserves the cortical circuitry associated with cardiac arousal during exercise in middle- to older-aged individuals. Observations of changes in heart rate (HR) and in cortical blood oxygenation level-dependent (BOLD) images were made in 52 healthy, active individuals (45-73 yr; 16 women, 36 men) across a range of fitness (26-66 ml·kg -1 ·min -1 ). Seven repeated bouts of isometric handgrip (IHG) at 40% maximal voluntary contraction force were performed with functional magnetic resonance imaging at 3 T, with each contraction lasting 20 s and separated by 40 s of rest. HR responses to IHG showed high variability across individuals. Linear regression revealed that cardiorespiratory fitness was not a strong predictor of the HR response ( r 2  = 0.09). In a region-of-interest analysis both the IHG task and the HR time course correlated with increased cortical activation in the bilateral insula and decreased activation relative to baseline in the anterior and posterior cingulate and medial prefrontal cortex (MPFC). t -Test results revealed greater deactivation at the MPFC with higher fitness levels beyond that of guideline-based activity. Therefore, whereas high cardiorespiratory fitness failed to affect absolute HR responses to IHG in this age range, a select effect was observed in cortical regions known to be associated with cardiovascular arousal. NEW & NOTEWORTHY Our first observation suggests that fitness does not strongly predict the heart rate (HR) response to a volitional handgrip task in middle- to older-aged adults. Second, the BOLD response associated with the handgrip task, and with the HR time course, was associated with response patterns in the cortical autonomic network. Finally, whereas high cardiorespiratory fitness failed to affect absolute HR responses to isometric handgrip in this age range, a select effect was observed in cortical regions known to be associated with cardiovascular arousal, beyond that achieved through healthy active living., (Copyright © 2017 the American Physiological Society.)

The limbs constitute the sole interface with the ground during most waking activities in mammalian species; it is therefore expected that somatosensory inputs from the limbs provide important information to the central nervous system for balance control. In the decerebrate cat model, the activity of a subset of neurons in the vestibular nuclei (VN) has been previously shown to be modulated by hindlimb movement. However, decerebration can profoundly alter the effects of sensory inputs on the activity of brain stem neurons, resulting in epiphenomenal responses. Thus, before this study, it was unclear whether and how somatosensory inputs from the limb affected the activity of VN neurons in conscious animals. We recorded brain stem neuronal activity in the conscious cat and characterized the responses of VN neurons to flexion and extension hindlimb movements and to whole body vertical tilts (vestibular stimulation). Among 96 VN neurons whose activity was modulated by vestibular stimulation, the firing rate of 65 neurons (67.7%) was also affected by passive hindlimb movement. VN neurons in conscious cats most commonly encoded hindlimb movement irrespective of the direction of movement (n = 33, 50.8%), in that they responded to all flexion and extension movements of the limb. Other VN neurons overtly encoded information about the direction of hindlimb movement (n = 27, 41.5%), and the remainder had more complex responses. These data confirm that hindlimb somatosensory and vestibular inputs converge onto VN neurons of the conscious cat, suggesting that VN neurons integrate somatosensory inputs from the limbs in computations that affect motor outflow to maintain balance., (Copyright © 2016 the American Physiological Society.)

It is well established that the cortical processing of somatosensory and auditory signals is attenuated when they result from self-generated actions compared with external events. This phenomenon is thought to result from an efference copy of motor commands used to predict the sensory consequences of an action through a forward model. The present work examined whether attenuation also takes place for visual reafferent signals from the moving limb during voluntary reaching movements. To address this issue, EEG activity was recorded in a condition in which visual feedback of the hand was provided in real time and compared with a condition in which it was presented with a 150-ms delay, thus creating a mismatch between the predicted and actual visual consequences of the movement. Results revealed that the amplitude of the N1 component of the visual event-related potential evoked by hand visual feedback over the parietal cortex was significantly smaller when presented in real time compared with when it was delayed. These data suggest that the cortical processing of visual reafferent signals is attenuated when they are correctly predicted, likely as a result of a forward model., (Copyright © 2016 the American Physiological Society.)

It has been shown that during the planning of a voluntary movement the transmission of cutaneous afferent inputs to the somatosensory cortex is attenuated shortly before the motor output as well as during movement execution. However, it is not known whether the sensory suppression observed during the planning phase (i.e., before any movement execution) is a systemic phenomenon or whether it is dependent on movement context. For example, movements such as step initiation are controlled based on information received from cutaneous receptors in the feet. Because afferent information emerging from these receptors is critical for movement initiation, we hypothesized that suppression of these inputs may not occur during the planning phase prior to gait initiation. To examine this hypothesis we measured the cortical response to somatosensory stimulation during the planning phase of step initiation and during movement execution. Sensitivity to cutaneous stimulation was assessed by measuring the amplitude of the cortical somatosensory-evoked potential (SEP, over the Cz electrode) following electrical stimulations of the plantar sole of one foot. Two stimulations were provided during the planning phase of a step movement and two stimulations during movement execution. It was found that the P50-N80 SEP was facilitated in the early planning phase (-700 ms before motor execution) compared with when participants remained still (control standing task). This mechanism might contribute to an enhanced perception of cutaneous input leading to a more accurate setting of the forces to be exerted onto the ground to shift the body's weight toward the supporting side prior to foot-off., (Copyright © 2015 the American Physiological Society.)

Changes in brain temperature can alter electrical properties of neurons and cause changes in behavior. However, it is not well understood how behaviors, like locomotion, or experimental manipulations, like anesthesia, alter brain temperature. We implanted thermocouples in sensorimotor cortex of mice to understand how cortical temperature was affected by locomotion, as well as by brief and prolonged anesthesia. Voluntary locomotion induced small (∼ 0.1 °C) but reliable increases in cortical temperature that could be described using a linear convolution model. In contrast, brief (90-s) exposure to isoflurane anesthesia depressed cortical temperature by ∼ 2 °C, which lasted for up to 30 min after the cessation of anesthesia. Cortical temperature decreases were not accompanied by a concomitant decrease in the γ-band local field potential power, multiunit firing rate, or locomotion behavior, which all returned to baseline within a few minutes after the cessation of anesthesia. In anesthetized animals where core body temperature was kept constant, cortical temperature was still > 1 °C lower than in the awake animal. Thermocouples implanted in the subcortex showed similar temperature changes under anesthesia, suggesting these responses occur throughout the brain. Two-photon microscopy of individual blood vessel dynamics following brief isoflurane exposure revealed a large increase in vessel diameter that ceased before the brain temperature significantly decreased, indicating cerebral heat loss was not due to increased cerebral blood vessel dilation. These data should be considered in experimental designs recording in anesthetized preparations, computational models relating temperature and neural activity, and awake-behaving methods that require brief anesthesia before experimental procedures., (Copyright © 2015 the American Physiological Society.)

This study of chronic incomplete spinal cord injury (SCI) subjects investigated patterns of central motor drive (i.e., central activation) of the plantar flexors using interpolated twitches, and modulation of soleus H-reflexes during lengthening, isometric, and shortening muscle actions. In a recent study of the knee extensors, SCI subjects demonstrated greater central activation ratio (CAR) values during lengthening (i.e., eccentric) maximal voluntary contractions (MVCs), compared with during isometric or shortening (i.e., concentric) MVCs. In contrast, healthy controls demonstrated lower lengthening CAR values compared with their isometric and shortening CARs. For the present investigation, we hypothesized SCI subjects would again produce their highest CAR values during lengthening MVCs, and that these increases in central activation were partially attributable to greater efficacy of Ia-α motoneuron transmission during muscle lengthening following SCI. Results show SCI subjects produced higher CAR values during lengthening vs. isometric or shortening MVCs (all P < 0.001). H-reflex testing revealed normalized H-reflexes (maximal SOL H-reflex-to-maximal M-wave ratios) were greater for SCI than controls during passive (P = 0.023) and active (i.e., 75% MVC; P = 0.017) lengthening, suggesting facilitation of Ia transmission post-SCI. Additionally, measures of spinal reflex excitability (passive lengthening maximal SOL H-reflex-to-maximal M-wave ratio) in SCI were positively correlated with soleus electromyographic activity and CAR values during lengthening MVCs (both P < 0.05). The present study presents evidence that patterns of dynamic muscle activation are altered following SCI, and that greater central activation during lengthening contractions is partly due to enhanced efficacy of Ia-α motoneuron transmission., (Copyright © 2015 the American Physiological Society.)

Primates are able to track small moving visual targets using smooth pursuit eye movements. Target motion for smooth pursuit is signaled by neurons in visual cortical areas MT and MST. In this study, we trained monkeys to either initiate or withhold smooth pursuit in the presence of a moving target to test whether this decision was reflected in the relative strength of "go" and "no-go" processes. We found that the gain of the motor response depended strongly on whether monkeys were instructed to initiate or withhold pursuit, thus demonstrating voluntary control of pursuit initiation. We found that the amplitude of the neuronal response to moving targets in areas MT and MST was also significantly lower on no-go trials (by 2.1 spikes/s on average). The magnitude of the neural response reduction was small compared with the behavioral gain reduction. There were no significant differences in neuronal direction selectivity, spatial selectivity, or response reliability related to pursuit initiation or the absence thereof. Variability in eye speed was negatively correlated with firing rate variability after target motion onset during go trials but not during no-go trials, suggesting that MT and MST activity represents an error signal for a negative feedback controller. We speculate that modulation of the visual motion signals in areas MT and MST may be one of the first visual cortical events in the initiation of smooth pursuit and that the small early response modulation may be amplified to produce an all-or-none motor response by downstream areas., (Copyright © 2015 the American Physiological Society.)

Two frequency peaks of variable preponderance have been reported for human physiological finger tremor. The high-frequency peak (20-25 Hz, seen only in postural tremor) is generally attributed to mechanical resonance, whereas the lower frequency peak (8-12 Hz, seen in both postural and kinetic tremor) is usually attributed to synchronous central or reflexive neural drive. In this study, we determine whether mechanical resonance could generate both peaks. In relaxed subjects, an artificial finger tremor was evoked by random mechanical perturbations of the middle finger or random electrical muscular stimulation of the finger extensor muscle. The high and the low frequencies observed in physiological tremor could both be created by either type of artificial input at appropriate input intensity. Resonance, inferred from cross-spectral gain and phase, occurred at both frequencies. To determine any neural contribution, we compared truly passive subjects with those who exhibited some electromyographic (EMG) activity in the finger extensor; artificially created tremor spectra were almost identical between groups. We also applied electrical stimuli to two clinically deafferented subjects lacking stretch reflexes. They exhibited the same artificial tremor spectrum as control subjects. These results suggest that both typical physiological finger tremor frequencies can be reproduced by random artificial input; neither requires synchronized neural input. We therefore suggest that mechanical resonance could generate both dominant frequency peaks characteristic of physiological finger tremor. The inverse relationship between the input intensity and the resulting tremor frequency can be explained by a movement-dependent reduction in muscle stiffness, a conjecture we support using a simple computational model., (Copyright © 2015 the American Physiological Society.)

Involuntarily exercising rats undergo more physical and mental stress than voluntarily exercising rats; however, these findings still lack electrophysiological evidence. Many studies have reported that theta rhythm appears when there is mental stress and that it is affected by emotional status. Thus we hypothesized that the differences between voluntary and involuntary movement should also exist in the hippocampal theta rhythm. Using the wheel and treadmill exercise models as voluntary and involuntary exercise models, respectively, this study wirelessly recorded the hippocampal electroencephalogram, electrocardiogram, and three-dimensional accelerations of young male rats. Treadmill and wheel exercise produced different theta patterns in the rats before and during running. Even though the waking baselines for the two exercise types were recorded in different environments, there did not exist any significant difference after distinguishing the rats' sleep/wake status. When the same movement-related parameters are considered, the treadmill running group showed more changes in their theta frequency (4-12 Hz), in their theta power between 9.5-12 Hz, and in their heart rate than the wheel running group. A positive correlation between the changes in high-frequency (9.5-12 Hz) theta power and heart rate was identified. Our results reveal various voluntary and involuntary changes in hippocampal theta rhythm as well as divergences in heart rate and high-frequency theta activity that may represent the effects of an additional emotional state or the sensory interaction during involuntary running by rats., (Copyright © 2014 the American Physiological Society.)

Human volitional actions are preceded by preparatory processes, a critical mental process of cognitive control for future behavior. Volitional action preparation is regulated by large-scale neural circuits including the cerebral cortex and the basal ganglia. Because volitional action preparation is a covert process, the network dynamics of such neural circuits have been examined by neuroimaging and recording event-related potentials. Here, we examined whether such covert processes can be measured by the overt responses of fixational saccades (including microsaccades), the largest miniature eye movements that occur during eye fixation. We analyzed fixational saccades while adult humans maintained fixation on a central visual stimulus as they prepared to generate a volitional saccade in response to peripheral stimulus appearance. We used the antisaccade paradigm, in which subjects generate a saccade toward the opposite direction of a peripheral stimulus. Appropriate antisaccade performance requires the following two aspects of volitional control: 1) facilitation of saccades away from the stimulus and 2) suppression of inappropriate saccades toward the stimulus. We found that fixational saccades that occurred before stimulus appearance reflected the dual preparatory states of saccade facilitation and suppression and correlated with behavioral outcome (i.e., whether subjects succeeded or failed to cancel inappropriate saccades toward the stimulus). Moreover, fixational saccades explained a large proportion of individual differences in behavioral performance (poor/excellent) across subjects. These results suggest that fixational saccades predict the outcome of future volitional actions and may be used as a potential biomarker to detect people with difficulties in volitional action preparation.

For the past five decades there has been wide acceptance of a relationship between the firing rate of motor units and the afterhyperpolarization of motoneurons. It has been promulgated that the higher-threshold, larger-soma, motoneurons fire faster than the lower-threshold, smaller-soma, motor units. This relationship was based on studies on anesthetized cats with electrically stimulated motoneurons. We questioned its applicability to motor unit control during voluntary contractions in humans. We found that during linearly force-increasing contractions, firing rates increased as exponential functions. At any time and force level, including at recruitment, the firing rate values were inversely related to the recruitment threshold of the motor unit. The time constants of the exponential functions were directly related to the recruitment threshold. From the Henneman size principle it follows that the characteristics of the firing rates are also related to the size of the soma. The "firing rate spectrum" presents a beautifully simple control scheme in which, at any given time or force, the firing rate value of earlier-recruited motor units is greater than that of later-recruited motor units. This hierarchical control scheme describes a mechanism that provides an effective economy of force generation for the earlier-recruited lower force-twitch motor units, and reduces the fatigue of later-recruited higher force-twitch motor units-both characteristics being well suited for generating and sustaining force during the fight-or-flight response.

Agonist-mediated reciprocal inhibition (RI) in distal skeletal muscles is an important neurophysiological phenomenon leading to improved movement coordination and efficiency. It has been shown to be reduced in aged and clinical populations, so the development of interventions augmenting RI is an important research goal. We examined the efficacy of using chronic passive muscle stretching to augment RI. The influence of 3 wk of plantarflexor stretching (4 × 30 s, two times/day) on RI of soleus and gastrocnemius initiated by tonic, voluntary dorsiflexion contractions [20% of maximum voluntary contraction (MVC)] was examined in 11 healthy men who performed stretch training and in nine nontraining controls. Hoffmann's reflexes (H-reflexes) were elicited by tibial nerve stimulation during both weak isometric (2% MVC) plantarflexions and dorsiflexion contractions at 20% MVC. Changes were examined at three joint angles, normalized to each subject's range of motion (ROM; plantarflexed = 10 ± 0°, neutral = -3.3 ± 2.9°, dorsiflexed = -16.5 ± 5.6°). No changes were detected in controls. A 20% increase in ROM in the stretch subjects was associated with a significant decrease in maximum H-reflex (H(max)): maximum evoked potential (M(max)), measured during 2% plantarflexion at the plantarflexed and neutral angles in soleus and at the plantarflexed angle in gastrocnemius (P < 0.05-0.01). By contrast, decreases in H(max):M(max) during 20% dorsiflexion contract were also seen at each angle in soleus and at the dorsiflexed angle in gastrocnemius. However, a greater decrease in H(max):M(max) measured during voluntary dorsiflexion rather than during plantarflexion, which indicates a specific change in RI, was detected only at the dorsiflexed angle (-30.7 ± 9.4% and -35.8 ± 6.8% for soleus and gastrocnemius, respectively). These results demonstrate the efficacy of soleus-gastrocnemius stretch training in increasing agonist-mediated RI from tibialis anterior onto soleus-gastrocnemius in young, healthy individuals at dorsiflexed, but not plantarflexed, joint angles.

We examined elbow muscle activities and movement kinematics to determine how subjects combine elementary control actions in performing movements with one and two trajectory segments. In reaching, subjects made a rapid elbow flexion to a visual target before stabilizing the limb with either a low or a higher level of elbow flexor/extensor coactivity (CoA), which was cued by target diameter. Cursor diameter provided real-time biofeedback of actual muscle CoA. In reversing, the limb was to reverse direction within the target and return to the origin with minimal CoA. We previously reported that subjects overshoot the goal when attempting a reversal after first having learned to reach accurately to the same target. Here we test the hypothesis that this hypermetria results because reversals co-opt the initial feedforward control action from the preceding trained reach, thereby failing to account for task-dependent changes in limb impedance induced by differences in flexor/extensor coactivity as the target is acquired (higher in reaching than reversing). Instructed increases in elbow CoA began mid-reach, thus increasing elbow impedance and reducing transient oscillations present in low CoA movments. Flexor EMG alone increased at movement onset. Test reversals incorporated the initial agonist activity of previous reaches but not the increased coactivity at the target, thus leading to overshoot. Moreover, we observed elevated coactivity in reversals upon returning to the origin even though coactivity in reaching was centered at the goal target. These findings refute the idea that the brain necessarily invokes distinct unitary control actions for reaches and reversals made to the same target. Instead, reaches and reversals share a common control action that initiates trajectories toward their target and another later control action that terminates movement and stabilizes the limb about its final resting posture, which differs in the two tasks.

The brain controls rhythmic movement through neural circuits combining visual information with proprioceptive information from the limbs. Although rhythmic movements are fundamental to everyday activities the specific details of the responsible control mechanisms remain elusive. We tested 39 young adults who performed flexion/extension movements of the forearm. We provided them with explicit knowledge of the amplitude and the speed of their movements, whereas frequency information was only implicitly available. In a series of 3 experiments, we demonstrate a tighter control of frequency compared with amplitude or speed. We found that in the absence of visual feedback, movements had larger amplitude and higher peak speed while maintaining the same frequency as when visual feedback was available; this was the case even when participants were aware of performing overly large and fast movements. Finally, when participants were asked to modulate continuously movement frequency, but not amplitude, we found the local coefficient of variability of movement frequency to be lower than that of amplitude. We suggest that a misperception of the generated amplitude in the absence of visual feedback, coupled with a highly accurate perception of generated frequency, leads to the performance of larger and faster movements with the same frequency when visual feedback is not available. Relatively low local coefficient of variability of frequency in a task that calls for continuous change in movement frequency suggests that we tend to operate at a constant frequency at the expense of variation in amplitude and peak speed.

This study investigated the potential influence of proximal sensory feedback on voluntary distal motor activity in the paretic upper limb of hemiparetic stroke survivors and the potential effect of voluntary distal motor activity on proximal muscle activity. Ten stroke subjects and 10 neurologically intact control subjects performed maximum voluntary isometric flexion and extension, respectively, at the metacarpophalangeal (MCP) joints of the fingers in two static arm postures and under three conditions of electrical stimulation of the arm. The tasks were quantified in terms of maximum MCP torque [MCP flexion (MCP(flex)) or MCP extension (MCP(ext))] and activity of targeted (flexor digitorum superficialis or extensor digitorum communis) and nontargeted upper limb muscles. From a previous study on the MCP stretch reflex poststroke, we expected stroke subjects to exhibit a modulation of voluntary MCP torque production by arm posture and electrical stimulation and increased nontargeted muscle activity. Posture 1 (flexed elbow, neutral shoulder) led to greater MCP(flex) in stroke subjects than posture 2 (extended elbow, flexed shoulder). Electrical stimulation did not influence MCP(flex) or MCP(ext) in either subject group. In stroke subjects, posture 1 led to greater nontargeted upper limb flexor activity during MCP(flex) and to greater elbow flexor and extensor activity during MCP(ext). Stroke subjects exhibited greater elbow flexor activity during MCP(flex) and greater elbow flexor and extensor activity during MCP(ext) than control subjects. The results suggest that static arm posture can modulate voluntary distal motor activity and accompanying muscle activity in the paretic upper limb poststroke.

The present study aimed to investigate neurophysiologic mechanisms mediating the newly discovered phenomenon of respiratory-motor interactions and to explore its potential clinical application for motor recovery. First, young and healthy subjects were instructed to breathe normally (NORM); to exhale (OUT) or inhale (IN) as fast as possible in a self-paced manner; or to voluntarily hold breath (HOLD). In experiment 1 (n = 14), transcranial magnetic stimulation (TMS) was applied during 10% maximal voluntary contraction (MVC) finger flexion force production or at rest. The motor-evoked potentials (MEPs) were recorded from flexor digitorum superficialis (FDS), extensor digitorum communis (EDC), and abductor digiti minimi (ADM) muscles. Similarly, in experiment 2 (n = 11), electrical stimulation (ES) was applied to FDS or EDC during the described four breathing conditions while subjects maintained 10%MVC of finger flexion or extension and at rest. In the exploratory clinical experiments (experiment 3), four patients with chronic neurological disorders (three strokes, one traumatic brain injury) received a 30-min session of breathing-controlled ES to the impaired EDC. In experiment 1, the EDC MEP magnitudes increased significantly during IN and OUT at both 10%MVC and rest; the FDS MEPs were enhanced only at 10%MVC, whereas the ADM MEP increased only during OUT, compared with NORM for both at rest and 10%MVC. No difference was found between NORM and HOLD for all three muscles. In experiment 2, when FDS was stimulated, force response was enhanced during both IN and OUT, but only at 10%MVC. When EDC was stimulated, force response increased at both 10%MVC and rest, only during IN, but not OUT. The averaged response latency was 83 ms for the finger extensors and 79 ms for the finger flexors. After a 30-min intervention of ES to EDC triggered by forced inspiration in experiment 3, we observed a significant reduction in finger flexor spasticity. The spasticity reduction lasted for ≥ 4 wk in all four patients. TMS and ES data, collectively, support the phenomenon that there is an overall respiration-related enhancement on the motor system, with a strong inspiration-finger extension coupling during voluntary breathing. As such, breathing-controlled electrical stimulation (i.e., stimulation to finger extensors delivered during the voluntary inspiratory phase) could be applied for enhancing finger extension strength and finger flexor spasticity reduction in poststroke patients.

The countermanding (or stop-signal) task, which requires the cancellation of an impending response on the infrequent presentation of a stop signal, enables study of the contextual control of movement generation and suppression. Here we present a novel and empirical measure of the time needed to cancel an impending gaze shift by recording neck muscle activity during a head-unrestrained oculomotor countermanding paradigm. On a subset of stop signal trials, subjects generated small head movements toward a target even though gaze remained stable due to a compensatory vestibular-ocular reflex. On such trials, we observed a burst of antagonist neck muscle activity during the small head-only error. Such antagonist neck muscle activity served as an active braking pulse as its magnitude scaled with the kinematics of the head-only error. This activity was selective for trials in which the head was arrested in mid-flight and did not appear on trials without a stop signal, on noncancelled stop signal trials when the gaze shift was completed, or on stop signal trials without head motion. Importantly, the timing of this antagonist activity related best to the onset of the stop signal (lagging it by ∼180 ms), and strongly correlated with behavioral estimates of the time needed to cancel a movement (the stop signal reaction time). These results are consistent with the notion that such selective antagonist neck muscle activity arises as a peripheral expression of the oculomotor stop process that successfully cancelled the gaze shift. Studying movement cancellation within nested systems like the head-unrestrained gaze shifting system offers a unique opportunity for investigating underlying neural mechanisms as the overall goal (i.e., to cancel a gaze shift) can be achieved despite motion of other components; on such individual trials, the oculomotor stop process is expressed as an active braking pulse.

Flexor digitorum profundus (FDP), the sole flexor of the fingertips, is critical for tasks such as grasping. It is a compartmentalized multitendoned muscle with both neural and mechanical links between the fingers. We determined whether voluntary activation (VA), the level of neural drive to muscle, could be measured separately in its four compartments, whether VA differed between the fingers, and whether maximal voluntary contraction (MVC) force and VA changed when the non-test fingers were extended from full flexion to 90° flexion to partially "disengage" the test finger. Transcranial magnetic stimulation (TMS) of the motor cortex was used to measure VA, in a position in which only FDP generated force at the fingertip. Despite differences among the fingers in MVCs, VA for each finger was ∼92% (n = 8), with no differences between fingers. When the test finger was partially disengaged by extending the other fingers to 90° flexion, performance was more variable both within and between subjects. MVCs decreased significantly by about 25-40% for the four fingers. However, VA was not significantly changed (n = 6) and was similar for the four fingers. In both positions, there were strong linear relationships between the voluntary forces and the superimposed twitch sizes, indicating that the method to measure VA was very reliable. Our results indicate that maximal VA is similar for all four compartments of FDP when force production by the other fingers is unconstrained. When altered mechanical connections between the compartments decrease voluntary force output there is little difference in neural drive.

Although the nature of gaze control regulating single saccades is relatively well documented, how such control is implemented to regulate multisaccade gaze shifts is not known. We used highly eccentric targets to elicit multisaccade gaze shifts and tested the ability of subjects to control the saccade sequence by presenting a second target on random trials. Their response allowed us to test the nature of control at many levels: before, during, and between saccades. Although the saccade sequence could be inhibited before it began, we observed clear signs of truncation of the first saccade, which confirmed that it could be inhibited in midflight as well. Using a race model that explains the control of single saccades, we estimated that it took about 100 ms to inhibit a planned saccade but took about 150 ms to inhibit a saccade during its execution. Although the time taken to inhibit was different, the high subject-wise correlation suggests a unitary inhibitory control acting at different levels in the oculomotor system. We also frequently observed responses that consisted of hypometric initial saccades, followed by secondary saccades to the initial target. Given the estimates of the inhibitory process provided by the model that also took into account the variances of the processes as well, the secondary saccades (average latency approximately 215 ms) should have been inhibited. Failure to inhibit the secondary saccade suggests that the intersaccadic interval in a multisaccade response is a ballistic stage. Collectively, these data indicate that the oculomotor system can control a response until a very late stage in its execution. However, if the response consists of multiple movements then the preparation of the second movement becomes refractory to new visual input, either because it is part of a preprogrammed sequence or as a consequence of being a corrective response to a motor error.

The goal of this study was to determine whether the activity of neurons in the supplementary eye field (SEF) is sufficient to control saccade initiation in macaque monkeys performing a saccade countermanding (stop signal) task. As previously observed, many neurons in the SEF increase the discharge rate before saccade initiation. However, when saccades are canceled in response to a stop signal, effectively no neurons with presaccadic activity display discharge rate modulation early enough to contribute to saccade cancellation. Moreover, SEF neurons do not exhibit a specific threshold discharge rate that could trigger saccade initiation. Yet, we observed more subtle relations between SEF activation and saccade production. The activity of numerous SEF neurons was correlated with response time and varied with sequential adjustments in response latency. Trials in which monkeys canceled or produced a saccade in a stop signal trial were distinguished by a modest difference in discharge rate of these SEF neurons before stop signal or target presentation. These findings indicate that neurons in the SEF, in contrast to counterparts in the frontal eye field and superior colliculus, do not contribute directly and immediately to the initiation of visually guided saccades. However the SEF may proactively regulate saccade production by biasing the balance between gaze-holding and gaze-shifting based on prior performance and anticipated task requirements.

Our ability to prepare an action in advance allows us to respond to our environment quickly, accurately, and flexibly. Here, we used event-related functional MRI to measure human brain activity while subjects maintained an active state of preparedness. At the beginning of each trial, subjects were instructed to prepare a pro- or antisaccade to a visual cue that was continually present during a long and variable preparation interval, but to defer the saccade's execution until a go signal. The deferred saccade task eliminated the mnemonic component inherent in memory-guided saccade tasks and placed the emphasis entirely on advance motor preparation. During the delay while subjects were in an active state of motor preparedness, the blood oxygen level-dependent signal in the frontal cortex showed 1) a sustained elevation throughout the preparation interval; 2) a linear increase with increasing delay length; 3) a bias for contra- rather than ipsiversive movements; 4) greater activity when the specific metrics of the planned saccade were known compared with when they were not; and 5) increased activity when the saccade was directed toward an internal versus an external representation (i.e., anticue location). These findings support the hypothesis that both the human frontal and parietal cortices are involved in the spatial selection and preparation of saccades.

Neurophysiological, neuroimaging, and lesion studies point to a highly distributed processing of temporal information by cortico-basal ganglia-thalamic networks. However, there are virtually no experimental data on the encoding of behavioral time by simultaneously recorded cortical ensembles. We predicted temporal intervals from the activity of hundreds of neurons recorded in motor and premotor cortex as rhesus monkeys performed self-timed hand movements. During the delay periods, when animals had to estimate temporal intervals and prepare hand movements, neuronal ensemble activity encoded both the time that elapsed from the previous hand movement and the time until the onset of the next. The neurons that were most informative of these temporal intervals increased or decreased their rates throughout the delay until reaching a threshold value, at which point a movement was initiated. Variability in the self-timed delays was explainable by the variability of neuronal rates, but not of the threshold. In addition to predicting temporal intervals, the same neuronal ensemble activity was informative for generating predictions that dissociated the delay periods of the task from the movement periods. Left hemispheric areas were the best source of predictions in one bilaterally implanted monkey overtrained to perform the task with the right hand. However, after that monkey learned to perform the task with the left hand, its left hemisphere continued and the right hemisphere started contributing to the prediction. We suggest that decoding of temporal intervals from bilaterally recorded cortical ensembles could improve the performance of neural prostheses for restoration of motor function.

Knee movements play a critical role in most balance corrections. Loss of knee flexibility may cause postural instability. Conversely, trained voluntary knee flexions executed during balance corrections might help to overcome balance deficits. We examined whether bilateral knee flexion could be added to automatic balance corrections generated by sudden balance perturbations. We investigated how this could be achieved and whether it improved or worsened balance control. Twenty-four healthy subjects participated in three different test conditions, in which they had to flex their knees following an auditory cue (VOLUNTARY condition), had to restore their balance in response to multidirectional rotations of a support surface (REACTIVE condition), or the combination of these two (COMBINED condition). A new variable set (PREDICTED), calculated as the mathematical sum of VOLUNTARY and REACTIVE, was compared with the COMBINED variable set. COMBINED responses following forward rotations were close to PREDICTED, or greater, suggesting adequate integration of knee flexion into the automatic balance reactions. For backward rotations, the COMBINED condition resulted in several near-falls, and this was generally associated with smaller knee flexion and smaller EMG responses. Subjects compensated by using greater trunk flexion and arm movements. Activity in several muscles displayed earlier onsets for the COMBINED condition following backward rotations. We conclude that healthy adults can incorporate voluntary knee flexion into their automatic balance corrections and that this depends on the direction of the postural perturbation. These findings highlight the flexibility of the human balance repertoire and underscore both the advantages and limitations of using trained voluntary movements to aid balance corrections in man.

To plan a reaching movement, the brain must integrate information about the location of the target with information about the limb selected for the reach. Here, we applied rapid event-related 3-T fMRI to investigate this process in human subjects (n = 16) preparing a reach following two successive visual instruction cues. One cue instructed which arm to use; the other cue instructed the location of the reach target. We hypothesized that regions involved in the integration of target and effector information should not only respond to each of the two instruction cues, but should respond more strongly to the second cue due to the added integrative processing to establish the reach plan. We found bilateral regions in the posterior parietal cortex, the premotor cortex, the medial frontal cortex, and the insular cortex to be involved in target-arm integration, as well as the left dorsolateral prefrontal cortex and an area in the right lateral occipital sulcus to respond in this manner. We further determined the functional properties of these regions in terms of spatial and effector specificity. This showed that the posterior parietal cortex and the dorsal premotor cortex specify both the spatial location of a target and the effector selected for the response. We therefore conclude that these regions are selectively engaged in the neural computations for reach planning, consistent with the results from physiological studies in nonhuman primates.

The tongue participates in a range of complex oromotor behaviors, including mastication, swallowing, respiration, and speech. Previous electromyographic studies of the human tongue have focused on respiratory-related tongue muscle activities and their role in maintaining upper airway patency. Remarkably, the activities of human hypoglossal motor units have not been studied during the execution of voluntary maneuvers. We recorded single motor unit activity using tungsten microelectrodes in the genioglossus muscle of 10 healthy human subjects performing both slow tongue protrusions and a static holding maneuver. Displacement of the tongue was detected by an isotonic transducer coupled to the lingual surface through a customized lever arm. For protrusion trials, the firing rate at recruitment was 13.1 +/- 3 Hz and increased steeply to an average of 24 +/- 6 Hz, often with very modest increases in tongue protrusion. For the static holding task, the average firing rate was 16.1 +/- 4 Hz, which is surprisingly high relative to limb motor units. The average coefficient of variation of interspike intervals was approximately 20% (range, 10-28%). These are the first recordings of their type obtained in human subjects and provide an initial glimpse into the voluntary control of hypoglossal motoneurons during tongue movements presumably instigated by activity in the motor cortex.

Intense itch and urge to scratch are the major symptoms of many chronic skin ailments, which are increasingly common. Vicious itch-scratch cycles are readily established and may diminish quality of life for those afflicted. We investigated peripheral and central processing of two types of itch sensation elicited by skin-prick tests of histamine and allergen solutions. Itch-related skin blood flow changes were measured by laser Doppler in 14 subjects responsive to type I allergens and 14 nonatopic subjects. In addition, this study examined central processing of both types of itch using functional magnetic resonance imaging (fMRI). Itch perception and blood flow changes were significantly greater when itch was induced by allergens compared with histamine. Both types of itch correlated significantly with activity in the genual anterior cingulate, striatum, and thalamus. Moreover, itch elicited by allergens activated orbitofrontal, supplementary motor, and posterior parietal areas. Histamine-induced itch also significantly correlated with activation in the insula bilaterally. The identification of limbic and ventral prefrontal activation in two types of itch processing likely reflects the subjects' desire to relieve the itch sensation by scratching, and these regions have been repeatedly associated with motivation processing. A dysfunction of the striato-thalamo-orbitofrontal circuit is believed to underlie the failure to regulate motivational drive in disorders associated with strong urges, e.g., addiction and obsessive compulsive disorder. The patterns of itch-induced activation reported here may help explain why chronic itch sufferers frequently self-harm through uncontrollable itch-scratch cycles.

Smooth pursuit (SP)-related neurons in the dorsal-medial part of medial superior temporal cortex (MSTd) carry extraretinal signals that may play a role in maintenance of SP once eye velocity matches target velocity. For example, it has not been determined whether the extraretinal signals reflect volitional SP commands or proprioception. The aim of this study was to test some potential sources of extraretinal signals in MSTd pursuit neurons. We tested 40 MSTd neurons during step-ramp SP with target blink conditions to show that they carried an extraretinal signal. To examine potential contributions from eye movements that might reflect proprioceptive feedback from eye muscles, we tested MSTd neurons during rotational vestibular ocular reflex in complete darkness (VORd). Vestibular stimulation was delivered in the earth horizontal plane to elicit reflex driven smooth eye movements that matched the speed and frequency of volitional SP. We also tested VOR in the light (VOR x 1) and cancellation of the VOR (VOR x 0). Our neurons were modulated during both SP and cancellation of the VOR. In contrast, MSTd smooth pursuit neurons with extraretinal signals were not significantly modulated during VORd (sensitivity < or = 0.10 spike/s/ degrees /s). This combination of properties is compatible with classifying these neurons as gaze-velocity related. Absence of modulation during VORd testing could be caused by cancellation of head and eye movement sensitivity or dependence of neuronal firing on volitional SP commands. Our results support the suggestion that modulation of SP-related MSTd neurons reflects volitional SP commands rather then eye movements generated by reflex pathways.

Volitional inhibition is the voluntary prevention of a prepared movement. Here we ask whether primary motor cortex (M1) is a site of convergence of cortical activity associated with movement preparation and volitional inhibition. Volitional inhibition was studied by presenting a stop signal before execution of an anticipated response that requires a key lift to intercept a revolving dial. Motor evoked potentials (MEPs) were elicited in intrinsic hand muscles by transcranial magnetic stimulation (TMS) to assess corticomotor excitability and short interval intracortical inhibition (sICI) during task performance. The closer the stop cue was presented to the anticipated response, the harder it was for subjects to inhibit their response. Corticomotor pathway excitability was temporally modulated during volitional inhibition. Using subthreshold TMS, corticomotor excitability was reduced for Stop trials relative to Go trials from 140 ms after the cue. sICI was significantly greater for Stop trials compared with Go trials at a time that preceded the onset of muscle activity associated with the anticipated response. These results provide evidence that volitional inhibition is exerted at a cortical level and that inhibitory networks within M1 contribute to volitional inhibition of prepared action.

A classic paradigm to study anticipatory pursuit consists in training monkeys to look at a target that appears in the center of a visual display, disappears during a short "gap" period, then reappears and immediately starts to move. To determine the role of prior directional information on anticipatory pursuit eye movements, we trained rhesus monkeys to associate the color of a centrally presented visual cue with the direction of an upcoming target motion. In a first experiment, a gap period occurred randomly in 50% of the trials. Consequently, two possible choices of timing of target motion onset were given to subjects to guide their anticipatory responses. In a second experiment, a gap period occurred during each trial and only a single choice of timing of target motion onset was given to subjects. We found that monkeys used the learned association between the color of the cue and the direction of future target motion to voluntarily initiate anticipatory pursuit movements in the appropriate direction. Anticipatory movements could be classified in two distinct populations: early and late movements. Early movements were most frequent when prior directional information was provided and when two choices of timing of target motion onset were given. The latency of visual pursuit was shortened and its velocity was larger when prior directional information was provided. We conclude that cognitive expectation of future target motion plays a dominant role in determining characteristics of anticipatory pursuit in the monkey.

This study investigated transmission of corticospinal output through motoneurons over a wide range of voluntary contraction strengths in humans. During voluntary contraction of biceps brachii, motor evoked potentials (MEPs) to transcranial magnetic stimulation of the motor cortex grow up to about 50% maximal force and then decrease. To determine whether the decrease reflects events at a cortical or spinal level, responses to stimulation of the cortex and corticospinal tract (cervicomedullary motor evoked potentials, CMEPs) as well as maximal M-waves (M(max)) were recorded during strong contractions at 50 to 100% maximum. In biceps and brachioradialis, MEPs and CMEPs (normalized to M(max)) evoked by strong stimuli decreased during strong elbow flexions. Responses were largest during contractions at 75% maximum and both potentials decreased by about 25% M(max) during maximal efforts (P < 0.001). Reductions were smaller with weaker stimuli, but again similar for MEPs and CMEPs. Thus the reduction in MEPs during strong voluntary contractions can be accounted for by reduced responsiveness of the motoneuron pool to stimulation. During strong contractions of the first dorsal interosseous, a muscle that increases voluntary force largely by frequency modulation, MEPs declined more than in either elbow flexor muscle (35% M(max), P < 0.001). This suggests that motoneuron firing rates are important determinants of evoked output from the motoneuron pool. However, motor cortical output does not appear to be limited at high contraction strengths.

We used a particular computational approach, the uncontrolled manifold hypothesis, to investigate joint angle covariation patterns during whole-body actions performed by standing persons. We hypothesized that two kinematic synergies accounted for the leg/trunk joint covariation across cycles during a rhythmic whole-body motion to stabilize two performance variables, the trunk orientation in the external space and the horizontal position of the center of mass (COM). Subjects stood on a force plate and performed whole-body rhythmic movements for 45 s under visual feedback on one of the four variables, the position of the center of pressure or the angle in one of the three joints (ankle, knee, or hip). The Fitts-like paradigm was used with two target amplitudes and six indices of difficulty (ID) for each of the four variables. This was done to explore the robustness of kinematic postural synergies. A speed-accuracy trade-off was observed in all feedback conditions such that the movement time scaled with ID and the scaling differed between the two movement amplitudes. Principal-component (PC) analysis showed the existence of a single PC in the joint space that accounted for over 95% of the joint angle variance. Analysis within the uncontrolled manifold hypothesis has shown that data distributions in the joint angle space were compatible with stabilization of both trunk orientation and COM location. We conclude that trunk orientation and the COM location are stabilized by co-varied changes of the major joint angles during whole-body movements. Despite the strong effects of movement amplitude and ID on performance, the structure of the joint variance showed only minor dependence on these task parameters. The two kinematic synergies (co-varied changes in the joint angles that stabilized the COM location and trunk orientation) have proven to be robust over a variety of tasks.

This study was designed to investigate the modulations of H-reflex and V-wave responses during passive and maximal active dynamic actions. Experiments were performed on 16 healthy males [age: 24 +/- 4 (SD) yr]. Maximal H-reflexes (Hmax) and M-waves (MmaxR) were evoked at the same muscle length during passive isometric, shortening and lengthening actions and during maximal voluntary isometric, concentric, and eccentric plantar-flexion. In all contraction types, supra-maximal stimulus intensity was used to evoke the superimposed maximal M wave (MmaxA) and V wave (V) of the soleus muscle. At rest, the Hmax/MmaxR ratio was significantly reduced during lengthening with respect to isometric and shortening actions (P < 0.05). For each action type, the ratio between H reflex superimposed to the contraction (Hsup) and MmaxA was not different from Hmax/MmaxR ratio. When plantar flexors were maximally voluntary activated, the Hsup/MmaxA ratio was still lower during eccentric contraction as compared with isometric and concentric efforts (0.33 +/- 0.03 vs. 0.47 +/- 0.02 and 0.50 +/- 0.03, P < 0.001), whereas V/MmaxA ratios were similar for all contraction types (isometric 0.26 +/- 0.02; concentric 0.23 +/- 0.03, and eccentric 0.24 +/- 0.02; P > 0.05). The V/MmaxA ratio was significantly lower than Hsup/MmaxA during isometric and concentric MVC (P < 0.001). No difference was observed between V/MmaxA and Hsup/MmaxA ratios during eccentric efforts. The H-reflex modulations, present during lengthening actions, were mainly attributed to presynaptic inhibition of Ia afferents and to homosynaptic postactivation depression. Results on V wave and H reflex suggest that during eccentric MVC, the spinal loop is specifically modulated by the supra-spinal centers and/or neural mechanisms at spinal level.

Recent studies of human arm movement have suggested that the control of stiffness may be important both for maintaining stability and for achieving differences in movement accuracy. In the present study, we have examined the voluntary control of postural stiffness in 3D in the human jaw. The goal is to address the possible role of stiffness control in both stabilizing the jaw and in achieving the differential precision requirements of speech sounds. We previously showed that patterns of kinematic variability in speech are systematically related to the stiffness of the jaw. If the nervous system uses stiffness control as a means to regulate kinematic variation in speech, it should also be possible to show that subjects can voluntarily modify jaw stiffness. Using a robotic device, a series of force pulses was applied to the jaw to elicit changes in stiffness to resist displacement. Three orthogonal directions and three magnitudes of forces were tested. In all conditions, subjects increased the magnitude of jaw stiffness to resist the effects of the applied forces. Apart from the horizontal direction, greater increases in stiffness were observed when larger forces were applied. Moreover, subjects differentially increased jaw stiffness along a vertical axis to counteract disturbances in this direction. The observed changes in the magnitude of stiffness in different directions suggest an ability to control the pattern of stiffness of the jaw. The results are interpreted as evidence that jaw stiffness can be adjusted voluntarily, and thus may play a role in stabilizing the jaw and in controlling movement variation in the orofacial system.

Different cerebellar regions participate in balance control and voluntary limb coordination, both of which might be important for normal bipedal walking. We wanted to determine the relative contributions of balance versus leg-coordination deficits to cerebellar gait ataxia in humans. We studied 20 subjects with cerebellar damage and 20 control subjects performing three tasks: a lateral weight-shifting task to measure balance, a visually guided stepping task to measure leg- coordination, and walking. We recorded three-dimensional joint position data during all tasks and center of pressure coordinates during weight-shifting. Each cerebellar subject was categorized as having no detectable deficits, a balance deficit only, a leg-placement deficit only, or both deficits. We then determined the walking abnormalities associated with each of these categories. Five of 10 measures of gait ataxia were abnormal in cerebellar subjects with a balance deficit, but only 1 was abnormal in cerebellar subjects with a leg-placement deficit. Furthermore, subjects with a balance deficit performed worse than subjects with a leg-placement deficit on 9 of the 10 gait measures. Finally, performance on the balance task, but not the leg-placement task, explained a significant proportion of the variance in walking speed for the entire cerebellar group. We conclude that balance deficits are more closely related to cerebellar gait ataxia than leg-placement deficits. Our findings are consistent with animal literature, which has suggested that cerebellar control of balance and gait are interrelated, and dissociable from cerebellar control of voluntary, visually guided limb movements.

Spinal cord injury may change both the distribution and the strength of the synaptic input within a motoneuron pool and therefore alter force gradation. Here, we have studied the relative contributions of motor unit recruitment and rate modulation to force gradation during voluntary contractions of thenar muscles performed by five individuals with chronic (>1 yr) cervical spinal cord injury. Mean +/- SD thenar unit firing rates were low during both steady-level 25% (8.3 +/- 2.2 Hz, n = 27 units) and 100% maximal voluntary contractions (MVCs, 9.2 +/- 3.1 Hz, n = 23 units). Thus modest rate modulation, or a lack of it in some units, was seen despite an average fourfold increase in integrated surface electromyographic activity and force. During ramp contractions, units were recruited at 5.7 +/- 2.5 Hz, but still only reached maximal firing rates of 12.8 +/- 4.9 Hz. Motor units were recruited up to 85% of the maximal force achieved (14.6 +/- 5.6 N). In contrast, unit recruitment in control hand muscles is largely complete by 30% MVC. Thus, during voluntary contractions of thenar muscles weakened by cervical spinal cord injury, motor unit rate modulation was limited and recruitment occurred over a wider than usual force range. Those motor units that were stopped voluntarily had significantly lower derecruitment versus recruitment thresholds. However, 8 units (24%) continued to fire long after the signal to end the voluntary contraction at a mean frequency of 5.9 +/- 0.8 Hz. The forces generated by this prolonged unit activity ranged from 0.3 to 7.2% maximum. Subjects were unable to stop this involuntary unit activity even with the help of feedback. The mechanisms that underlie this prolonged motor unit firing need to be explored further.

Previous research has shown that grip and load forces are modulated simultaneously during manipulation of a hand-held object. This close temporal coupling suggested that both forces are controlled by an internal model within the CNS that predicts the changes in tangential force on the fingers. The objective of the present study was to examine how the internal model would compensate for the loss of cutaneous sensation through local anesthesia of the index and thumb. Ten healthy adult subjects (5 men and 5 women aged 20-57 yr) were asked to grasp, lift, and hold stationary, a 250 g object for 20 s. Next, the subjects were asked to perform vertical oscillatory movements over a distance of 20 cm at a rate of 1.0 Hz for 30 s. Eleven trials were performed with intact sensation, and 11 trials after a local ring-block anesthesia of the index and thumb with bupivacain (5 mg/ml). During static holding, loss of cutaneous sensation produced a significant increase in the safety margin. However, the grip force declined significantly over the 20-s static hold period. During oscillatory arm movements, grip and load forces were continuously modulated together in a predictive manner as suggested by Flanagan and Wing. Again, the grip force declined over the 30-s movement, and 7/10 subjects dropped the object at least once. With intact sensation, the object was never dropped; but with the fingers anesthetized, it was dropped on 36% of the trials, and a significant slip occurred on a further 12%. The mean correlation between the grip and load forces for all subjects deteriorated from 0.71 with intact sensation to 0.48 after digital anesthesia. However, a cross-correlation calculated between the grip and load forces indicated that the phase lag was approximately zero both with and without digital anesthesia. Taken together, the data from the present study suggest that cutaneous afferents are required for setting and maintaining the background level of the grip force in addition to their phasic slip-detection function and their role in adapting the grip force/load force ratio to the friction on initial contact with an object. Finally, at a more theoretical level, they correct and maintain an internal model of the physical properties of hand-held objects.

We have examined the contribution of the red nucleus to the control of locomotion in the cat. Neuronal activity was recorded from 157 rubral neurons, including identified rubrospinal neurons, in three cats trained to walk on a treadmill and to step over obstacles attached to the moving belt. Of 72 neurons with a receptive field confined to the contralateral forelimb, 66 were phasically active during unobstructed locomotion. The maximal activity of the majority of neurons (59/66) was centered around the swing phase of locomotion. Slightly more than half of the neurons (36/66) were phasically activity during both swing and stance. In addition, some rubral neurons (14/66) showed multiple periods of phasic activity within the swing phase of the locomotor cycle. Periods of phasic discharge temporally coincident with the swing phase of the ipsilateral limb were observed in 7/66 neurons. During voluntary gait modifications, most forelimb-related neurons (70/72) showed a significant increase in their discharge activity when the contralateral limb was the first to step over the obstacle (lead condition). Maximal activity in nearly all cells (63/70) was observed during the swing phase, and 23/63 rubral neurons exhibited multiple increases of activity during the modified swing phase. A number of cells (18/70) showed multiple periods of increased activity during swing and stance. Many of the neurons (35/63, 56%) showed an increase in activity at the end of the swing phase; this period of activity was temporally coincident with the period of activity in wrist dorsiflexors, such as the extensor digitorum communis. A smaller proportion of neurons with receptive fields restricted to the hindlimbs showed similar characteristics to those observed in the population of forelimb-related neurons. The overall characteristics of these rubral neurons are similar to those that we obtained previously from pyramidal tract neurons recorded from the motor cortex during an identical task. However, in contrast to the results obtained in the rubral neurons, most motor cortical neurons showed only one period of increased activity during the step cycle. We suggest that both structures contribute to the modifications of the pattern of EMG activity that are required to produce the change in limb trajectory needed to step over an obstacle. However, the results suggest an additional role for the red nucleus in regulating intra- and interlimb coordination.

We report neck muscle activity and head movements evoked by electrical stimulation of the superior colliculus (SC) in head-unrestrained monkeys. Recording neck electromyography (EMG) circumvents complications arising from the head's inertia and the kinetics of muscle force generation and allows precise assessment of the neuromuscular drive to the head plant. This study served two main purposes. First, we sought to test the predictions made in the companion paper of a parallel drive from the SC onto neck muscles. Low-current, long-duration stimulation evoked both neck EMG responses and head movements either without or prior to gaze shifts, testifying to a SC drive to neck muscles that is independent of gaze-shift initiation. However, gaze-shift initiation was linked to a transient additional EMG response and head acceleration, confirming the presence of a SC drive to neck muscles that is dependent on gaze-shift initiation. We forward a conceptual neural architecture and suggest that this parallel drive provides the oculomotor system with the flexibility to orient the eyes and head independently or together, depending on the behavioral context. Second, we compared the EMG responses evoked by SC stimulation to those that accompanied volitional head movements. We found characteristic features in the underlying pattern of evoked neck EMG that were not observed during volitional head movements in spite of the seemingly natural kinematics of evoked head movements. These features included reciprocal patterning of EMG activity on the agonist and antagonist muscles during stimulation, a poststimulation increase in the activity of antagonist muscles, and synchronously evoked responses on agonist and antagonist muscles regardless of initial horizontal head position. These results demonstrate that the electrically evoked SC drive to the head cannot be considered as a neural replicate of the SC drive during volitional head movements and place important new constraints on the interpretation of electrically evoked head movements.

The goals of this study were to determine the degree to which subjects could voluntarily modulate static endpoint stiffness orientation and to quantify the effects of simultaneously generated voluntary endpoint forces on this ability. Static endpoint stiffness, which characterizes the relationship between externally imposed displacements of the hand and the elastic forces generated in response, was estimated in real time during the application of planar, stochastic perturbations of endpoint position. This estimation was accomplished using a real-time parametric identification algorithm on measured force and position data. Subjects were provided with real-time visual feedback of endpoint stiffness, and their ability to modulate the orientation of maximum static stiffness was measured for different endpoint force magnitudes and directions. We found that individuals can voluntarily change stiffness orientation but that the magnitude of these changes is small, the range of available stiffness orientations decreases as endpoint force exertion increases, and endpoint force direction significantly constrains direction and magnitude of the stiffness orientations that can be achieved. Given these findings it appears unlikely that static endpoint stiffness orientation is controlled independently of force by voluntary neural mechanisms during postural tasks.

We used event-related functional magnetic resonance imaging (fMRI) to measure brain activity when subjects were performing identical tasks in the context of either a task-set switch or a continuation of earlier performance. The context, i.e., switching or staying with the current task, influenced medial frontal cortical activation; the medial frontal cortex is transiently activated at the time that subjects switch from one way of performing a task to another. Two types of task-set-switching paradigms were investigated. In the response-switching (RS) paradigm, subjects switched between different rules for response selection and had to choose between competing responses. In the visual-switching (VS) paradigm, subjects switched between different rules for stimulus selection and had to choose between competing visual stimuli. The type of conflict, sensory (VS) or motor (RS), involved in switching was critical in determining medial frontal activation. Switching in the RS paradigm was associated with clear blood-oxygenation-level-dependent signal increases ("activations") in three medial frontal areas: the rostral cingulate zone, the caudal cingulate zone, and the presupplementary motor area (pre-SMA). Switching in the VS task was associated with definite activation in just one medial frontal area, a region on the border between the pre-SMA and the SMA. Subsequent to the fMRI session, we used MRI-guided frameless stereotaxic procedures and repetitive transcranial magnetic stimulation (rTMS) to test the importance of the medial frontal activations for task switching. Applying rTMS over the pre-SMA disrupted subsequent RS performance but only when it was applied in the context of a switch. This result shows, first, that the pre-SMA is essential for task switching and second that its essential role is transient and limited to just the time of behavioral switching. The results are consistent with a role for the pre-SMA in selecting between response sets at a superordinate level rather than in selecting individual responses. The effect of the rTMS was not simply due to the tactile and auditory artifacts associated with each pulse; rTMS over several control regions did not selectively disrupt switching. Applying rTMS over the SMA/pre-SMA area activated in the VS paradigm did not disrupt switching. This result, first, confirms the limited importance of the medial frontal cortex for sensory attentional switching. Second, the VS rTMS results suggest that just because an area is activated in two paradigms does not mean that it plays the same essential role in both cases.

The vestibuloocular reflex (VOR) effectively stabilizes the visual world on the retina over the wide range of head movements generated during daily activities by producing an eye movement of equal and opposite amplitude to the motion of the head. Although an intact VOR is essential for stabilizing gaze during walking and running, it can be counterproductive during certain voluntary behaviors. For example, primates use rapid coordinated movements of the eyes and head (gaze shifts) to redirect the visual axis from one target of interest to another. During these self-generated head movements, a fully functional VOR would generate an eye-movement command in the direction opposite to that of the intended shift in gaze. Here, we have investigated how the VOR pathways process vestibular information across a wide range of behaviors in which head movements were either externally applied and/or self-generated and in which the gaze goal was systematically varied (i.e., stabilize vs. redirect). VOR interneurons [i.e., type I position-vestibular-pause (PVP) neurons] were characterized during head-restrained passive whole-body rotation, passive head-on-body rotation, active eye-head gaze shifts, active eye-head gaze pursuit, self-generated whole-body motion, and active head-on-body motion made while the monkey was passively rotated. We found that regardless of the stimulation condition, type I PVP neuron responses to head motion were comparable whenever the monkey stabilized its gaze. In contrast, whenever the monkey redirected its gaze, type I PVP neurons were significantly less responsive to head velocity. We also performed a comparable analysis of type II PVP neurons, which are likely to contribute indirectly to the VOR, and found that they generally behaved in a quantitatively similar manner. Thus our findings support the hypothesis that the activity of the VOR pathways is reduced "on-line" whenever the current behavioral goal is to redirect gaze. By characterizing neuronal responses during a variety of experimental conditions, we were also able to determine which inputs contribute to the differential processing of head-velocity information by PVP neurons. We show that neither neck proprioceptive inputs, an efference copy of neck motor commands nor the monkey's knowledge of its self-motion influence the activity of PVP neurons per se. Rather we propose that efference copies of oculomotor/gaze commands are responsible for the behaviorally dependent modulation of PVP neurons (and by extension for modulation of the status of the VOR) during gaze redirection.

The aim of this study was to use time-resolved functional magnetic resonance imaging (fMRI) to investigate temporal differences in the activation of the supplementary motor area (SMA) and the primary motor cortex (M1). We report data from eight human volunteers who underwent fMRI examinations in a 1.5T Philips Gyroscan ACS-NT MRI scanner. While wearing a contact glove, subjects executed a complex automated sequence of finger movements either spontaneously or in response to external auditory cues. Based on the result of a functional scout scan, a single slice that included the M1 and the SMA was selected for image acquisition (echo planar imaging, repetition time 100 ms, echo time 50 ms, 64 x 64 matrix, 1,000 images). Data were analyzed with a shifting cross-correlation approach using the STIMULATE program and in-house programs written in Interactive Data Language (IDL(TM)). Time-course data were generated for regions of interest in the M1 as well as in the rostral and caudal SMA. Mean time between onset of the finger movement sequence and half-maximum of the signal change in M1 was 3.6 s for the externally cued execution (SD 0.5) and 3.5 s for the spontaneous execution (SD 0.6). Activation in the rostral section of the SMA occurred 0.7 s earlier than it did in the M1 during the externally cued execution and 2.0 s earlier during the spontaneous execution, a difference significant at the P < 0.01 level. Our results indicate that rostral SMA activation precedes M1 activation by varying time intervals in the sub-second range that are determined by the mode of movement initialization. By applying a paradigm that exerts a differential influence on temporal activation, we could ensure that the observed timing differences were not the result of differences in hemodynamic response function.

To study the functional role of synchronized neuronal activity in the human motor system, we simultaneously recorded cortical activity by high-resolution electroencephalography (EEG) and electromyographic (EMG) activity of the activated muscle during a phasic voluntary movement in seven healthy subjects. Here, we present evidence for dynamic beta-range (16-28 Hz) synchronization between cortical activity and muscle activity, starting after termination of the movement. In the same time range, increased tonic activity in the activated muscle was found. During the movement execution a low-frequency (2-14 Hz) synchronization was found. Using a novel analysis, phase-reference analysis, we were able to extract the EMG-coherent EEG maps for both, low- and high-frequency beta range synchronization. The electrical source reconstruction of the EMG-coherent EEG maps was performed with respect to the individual brain morphology from magnetic resonance imaging (MRI) using a distributed source model (cortical current density analysis) and a realistic head model. The generators of the beta-range synchronization were not only located in the primary motor area, but also in premotor areas. The generators of the low-frequency synchronization were also located in the primary motor and in premotor areas, but with additional participation of the medial premotor area. These findings suggest that the dynamic beta-range synchronization between multiple cortical areas and activated muscles reflects the transition of the collective motor network into a new equilibrium state, possibly related to higher demands on attention, while the low-frequency synchronization is related to the movement execution.

We present a new computational model for the development of task-specific focal dystonia. The purpose of the model is to explain how altered sensory representations can lead to abnormal motor behavior. Dystonia is described as the result of excessive gain through a sensorimotor loop. The gain is determined in part by the sensory cortical area devoted to each motor function, and behaviors that lead to abnormal increases in sensory cortical area are predicted to lead to dystonia. Properties of dystonia including muscular co-contraction, overflow movements, and task specificity are predicted by properties of a linear approximation to the loop transformation. We provide simulations of several different mechanisms that can cause the gain to exceed 1 and the motor activity to become sustained and uncontrolled. The model predicts that normal plasticity mechanisms may contribute to worsening of symptoms over time.

We studied the stability of changes in motor performance associated with adaptation to a novel dynamic environment during goal-directed movements of the dominant arm. Eleven normal, human subjects made targeted reaching movements in the horizontal plane while holding the handle of a two-joint robotic manipulator. This robot was programmed to generate a novel viscous force field that perturbed the limb perpendicular to the desired direction of movement. Following adaptation to this force field, we sought to determine the relative role of kinematic errors and dynamic criteria in promoting recovery from the adapted state. In particular, we compared kinematic and dynamic measures of performance when kinematic errors were allowed to occur after removal of the viscous fields, or prevented by imposing a simulated, mechanical "channel" on movements. Hand forces recorded at the handle revealed that when kinematic errors were prevented from occurring by the application of the channel, recovery from adaptation to the novel field was much slower compared with when kinematic aftereffects were allowed to take place. In particular, when kinematic errors were prevented, subjects persisted in generating large forces that were unnecessary to generate an accurate reach. The magnitude of these forces decreased slowly over time, at a much slower rate than when subjects were allowed to make kinematic errors. This finding provides strong experimental evidence that both kinematic and dynamic criteria influence motor adaptation, and that kinematic-dependent factors play a dominant role in the rapid loss of adaptation after restoring the original dynamics.

Although many studies have investigated reflexes after stimulation of either cutaneous or proprioceptive afferents, much less is known about responses after more natural perturbations, such as stumbling over an obstacle. In particular, the phase dependency of these responses and their relation to the stumbling behavior has received little attention. Hence response strategies during stumbling reactions after perturbations at different times in the swing phase of gait were studied. While subjects walked on a treadmill, a rigid obstacle unexpectedly obstructed the forward sway of the foot. All subjects showed an "elevating strategy" after early swing perturbations and a "lowering strategy" after late swing perturbations. During the elevating strategy, the foot was directly lifted over the obstacle through extra knee flexion assisted by ipsilateral biceps femoris (iBF) responses and ankle dorsiflexion assisted by tibialis anterior (iTA) responses. Later, large rectus femoris (iRF) activations induced knee extension to place the foot on the treadmill. During the lowering strategy, the foot was quickly placed on the treadmill and was lifted over the obstacle in the subsequent swing. Foot placement was actively controlled by iRF and iBF responses related to knee extension and deceleration of the forward sway. Activations of iTA mostly preceded the main ipsilateral soleus (iSO) responses. For both strategies, four response peaks could be distinguished with latencies of approximately 40 ms (RP1), approximately 75 ms (RP2), approximately 110 ms (RP3), and approximately 160 ms (RP4). The amplitudes of these response peaks depended on the phase in the step cycle. The phase-dependent modulation of the responses could not be accounted for by differences in stimulation or in background activity and therefore is assumed to be premotoneuronal in origin. In mid swing, both the elevating and lowering strategy could occur. For this phase, the responses of the two strategies could be compared in the absence of phase-dependent response modulation. Both strategies had the same initial electromyographic responses till approximately 100 ms (RP1-RP2) after perturbation. The earliest response (RP1) is assumed to be a short-latency stretch reflex evoked by the considerable impact of the collision, whereas the second (RP2) has features reminiscent of cutaneous and proprioceptive responses. Both these responses did not determine the behavioral response strategy. The functionally important response strategies depended on later responses (RP3-RP4). These data suggest that during stumbling reactions, as a first line of defense, the CNS releases a relatively aspecific response, which is followed by an appropriate behavioral response to avoid the obstacle.

A previous study has demonstrated that the soleus H reflex is facilitated in association with voluntary teeth clenching in proportion with biting force in humans. The present study tried to elucidate the functional significance of this facilitation of the soleus H reflex, by examining 1) whether the facilitation of the H reflex is reciprocal or nonreciprocal between the ankle extensors and flexors and 2) whether the reciprocal Ia inhibition of crural muscles is facilitated or depressed in association with voluntary teeth clenching. The H reflex of the pretibial muscles was evoked by stimulation of the common peroneal nerve in seven healthy subjects with no oral dysfunction. The pretibial H reflex was facilitated in association with voluntary teeth clenching in a force-dependent manner. The facilitation started preceding the onset of electromyographic activity of the masseter muscle. Stimulation of the common peroneal nerve at low intensities subthreshold for evoking the M wave of the pretibial muscles inhibited the soleus H reflex after a short latency corresponding with a disynaptic inhibition, indicating that the reciprocal Ia inhibition was depressed in association with voluntary teeth clenching. Thus, the present study has shown that voluntary teeth clenching evokes a nonreciprocal facilitation of ankle extensor and flexor muscles and attenuated reciprocal Ia inhibition from the pretibial muscles to the soleus muscle. It is concluded that voluntary teeth clenching contributes to improve stability of stance rather than smoothness of movements.

Experiments were done to determine whether the strength of reciprocal inhibition from ankle flexors to extensors can be controlled independently of the level of ongoing motor activity in a task-dependent manner. In this paper we use the term reciprocal inhibition in the functional sense--inhibition of the antagonist(s) during activity of the agonist(s)--without reference to specific neural pathways that may be involved. The strength of reciprocal inhibition of the soleus alpha-motoneurons was determined by measuring the amplitude of the H reflex during voluntary, postural, and locomotor tasks requiring activity of the ankle flexor tibialis anterior (TA). Differences in the strength of reciprocal inhibition between tasks were determined from plots of the soleus H reflex amplitude versus the mean value of the TA electromyogram (EMG). Additionally, in tasks involving movement, the correlation between the H reflex amplitude and the joint kinematics was calculated. In most subjects (15 of 22) the soleus H reflex decreased approximately linearly with increasing tonic voluntary contractions of the TA. The H reflex also decreased approximately linearly with the TA EMG activity when subjects where asked to lean backward. There were no statistical differences between the regression lines obtained in these tasks. In some subjects (7 of 22), however, the H reflex amplitude was independent of the level of TA EMG activity, except for a sudden drop at high levels of TA activity (approximately 60-80% of maximum voluntary contraction). The type of relation between the soleus H reflex and the TA EMG activity in these tasks was not correlated with the maximum H reflex to maximum M wave (Hmax/Mmax) ratio measured during quiet standing. In marked contrast, during the swing phase of walking--over the same range of TA EMG activity as during the tonic voluntary contraction task--the H reflex was reduced to zero in most subjects (24 of 31). In seven subjects the H reflex during the swing phase was reduced to some 5% of the value during quiet standing. The same result was found when subjects were asked to produce a stepping movement with one leg (OLS) in response to an auditory "go" signal. Additionally, in the OLS task it was possible to examine the behavior of the H reflex during the reaction time and thus to evaluate the relative contribution of central commands versus movement-related afferent activity to the inhibition of the soleus H reflex. In 11 of 12 subjects the H reflex attained its minimum value before either the onset of EMG activity or movement of any of the leg joints. It is significant that the H reflex was most powerfully inhibited during the swing phase of walking and the closely related OLS task. The H reflex was also measured during isolated ankle dorsiflexion movements. The subjects were asked to track a target displayed on a computer screen with dorsiflexion movements of the ankle. The trajectory of the target was the same as that of the ankle during the swing phase of walking. The soleus H reflexes were intermediate in size between the values obtained in the tonic contraction task and the walking or OLS tasks. A negative, but weak, correlation (r2 < 0.68) between the soleus H reflex and the TA EMG was found in 3 of 10 subjects. Furthermore, there was no correlation between the H reflex amplitude and the ankle angular displacement or angular velocity. In this task, as in the OLS task, the H reflex began to decrease during the reaction time before the onset of TA EMG activity. We conclude that the strength of reciprocal inhibition of the soleus alpha-motoneuron pool can thus be controlled independently of the level of motor activity in the ankle flexors. The strength of the inhibition of the antagonist(s) depends on the task, and for each task the strength of the inhibition is not necessarily proportional to the level of motor activity in the agonist(s). (ABSTRACT TRUNCATED)